Defence against Extracellular Pathogens

Question 1

What does the Fc region of immunoglobulins do while the Fab region is bound to an antigen

Answer 1

Works with other parts of the immune system

Question 2

Antibody Isotype interaction with defence components

Answer 2

Complement Activation - IgM, IgG

Phagocyte Binding - IgG, IgA

Mast Cell Binding - IgE

NK Cell Binding - IgG

Question 3

Complement

Answer 3

Collection of proteins found in the circulation and tissue fluids

The pathway occurs as a cascade with amplification

**described by ability to ‘complement’ the effects of antibodies

Question 4

What are some roles of complement proteins

Answer 4

Activation of Enymes
Direct Immune Responses
Control Proteins

Question 5

Describe the splitting in complement pathways

Answer 5

Activation steps involve splitting of complement proteins via enzymes (which may be other complement proteins)
e.g. C –> Ca + Cb

Question 6

Central Event of Compliment Activation

Answer 6

C3 -> C3a + C3b

Question 7

C3 Convertase Enzyme

Answer 7

Enzyme that splits C3 into C3a + C3b

There are 2 different C3 convertases

Question 8

C1q

Answer 8

Complement protein that binds to the Fc region of IgG (or IgM); likened to a bunch of tulips with 6 globular tips that can bind to the Fc regions with 6 stems

Only binds to bound IgG

Can bind to up to 6 antibodies

Part of Classical Pathway

Question 9

C1r, C1s

Answer 9

Activated and bound to C1q after its binding

Act as enzymes that can split C4 and C2; both into Cxa, Cxb

Question 10

Mannose binding leptase

Answer 10

Binds to Mannose residues on microbial carbohydrates (not antibodies)

It is associated with 4 other proteins (Mannose Binding Leptin Associated Proteases [MASP] 1, 2)

When MBL is activated, it activates MASP enzymes which can split C4, C2, forming the C3 convertase complex (C4b2a)

Part of MB-Lectin Pathway

Question 11

What happens to C2a and C4b

Answer 11

This forms a C4b2a complex; it is a C3 convertase enzyme

Question 12

Describe Alternative C3 Convertase Pathway

Answer 12

Trigerred by direct interaction of previously formed C3b (from ticking pathway) to microbial surfaces

When C3b is formed and binds, it binds another complement protein B fragment of factor B

Another stabilising protein P (properdin)

Leads to C3 Convertase:
C3bBbP

Question 13

How is there enough C3b for alternative pathway

Answer 13

Tiny amoutns of C3 are being constantly degraded by tissue proteases to generate C3a and C3b

Tickover Pathway

Question 14

What happens to C3b if unstabilised or stabilised

Answer 14

It is very unstable and very rapidly degrades into inactive fragments unless stablised; happens by binding to microbial surfaces which stablises it and allows it to form C3bBbP (so it only happens with infection)

Question 15

What happens if you bind either C3 convertase enzyme and bind them to another C3b

Answer 15

They become C5 convertase enzymes which split the protein into C5a and C5b

Question 16

What does C5b do

Answer 16

Forms part of the membrane attack pathway; interacts with C6, C7, C8 and C9 to bring about membrane lysis and form a tube that makes a pore on the pathogen’s surface, destroying the microbe as many hundreds of pores can be formed on one microbe

Question 17

Opsonins and examples

Answer 17

Molecules that make microbes more “attractive” to phagocytes which have specialised receptors for such opsonins

Mannan-binding lectin
C-reactive protein
Antibodies

Question 18

Describe opsonisation with antibodies

Answer 18

Microbes are bound to IgG proteins with their Fc regions sticking out

These IgG proteins activate classical complement pathway and lead to C3b being secreted onto surface of microbe

Phagocytes have Fc receptors; also receptors for C3b on surface of microbes

Opsonin and phagocyte interaction stronger than normal PRR and PAMP interaction

Surface membrane engulfs microbe and creates phagosome (vesicle containing microbe); merges with lysosome to form phagolysosome to release the enzymes and put them onto the microbe surface and bring about digestion/destruction

Question 19

How does digestion of foreign bodies too large to be engulfed by a cell

Answer 19

Eosinophils perform external digestion (done to stuff like worms)

They have C receptors and complement receptors on their surface

If we have a large parasitic helminth with antibodies on it and C3b; eosinophil can bind to parasite via complement and Fc receptors (Fc Gamma and Fc Epsilon)

When bound, eosinophils release digestive enzymes onto parasitic surface

Question 20

Describe location of mast cells

Answer 20

Tissue resident cells; not circulating but similar function to basophils

Question 21

What receptors do mast cells have expressed on their surface

Answer 21

High affinity Fc Epsilon receptors (IgE receptors)

Question 22

Why is IgE concentration high in tissue

Answer 22

IgE binds to mast cells largely so those antibodies diffuse into the tissues where they can bind

Question 23

How are mast cells activated

Answer 23

Either by the binding of an antigen (in tissue) to bound proteins or the binding of C3a & C5a onto complement receptors

Question 24

What happens when mast cells are activated

Answer 24

Immediately, they release the contents of vesicles that contain pre-made mediators (e.g. histamine, heparin, tryptase)

After a slightly longer time (5-30 mins), the mediators released later metabolise arachidonic acid into leukotrienes and prostaglandins which can then produce inflammatory cytokines

Question 25

Summaries the Local Inflammatory Response

Answer 25

Vasodilatation, Increased Vascular Permeability, Chemotaxis of WBCs, Immobilisation, Activation

Question 26

What does elevated C Reactive Protein Indicate

Answer 26

Systemic Inflammation

**Released from liver in response to IL6

Question 27

3 Examples of Cytokines produced during systemic inflammatory response

Answer 27

Interleukin 1
Interleukin 6
Tumour Necrosis Factor

Question 28

Cytokine Storm

Answer 28

Excessive amounts of inflammation brought about by infection that causes too many cytokines to be released that damage too much tissue and can cause organ failure; lethal

Symptom of severe Covid-19